title: MPTP-induced dopamine neuron degeneration and glia activation is potentiated in MDMA-pretreated mice.
abstract: Clinical observations report a greater propensity to develop Parkinson's disease (PD) in amphetamine users. 3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is an amphetamine-related drug that is largely consumed by adolescents and young adults, which may have neuroinflammatory and neurotoxic effects. Here, the objective was to evaluate in mice whether consumption of MDMA during adolescence might influence the neuroinflammatory and neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin known to induce PD in humans. The activation of astroglia and microglia by glial fibrillary acidic protein (GFAP) and complement receptor type 3 (CD11b) immunohistochemistry and the degeneration of dopaminergic neurons by tyrosine hydroxylase (TH) immunohistochemistry were evaluated. MPTP (20 mg/kg × 4) was administered to mice treated from ages 8 weeks to 17 weeks with MDMA (10 mg/kg twice daily, two times a week). In mice that were chronically treated with MDMA, administration of MPTP induced a higher microglial and astroglial response in both the striatum and the substantia nigra pars compacta (SNc) compared with vehicle-treated or vehicle + MPTP-treated mice. Inflammatory changes were associated with a decrease in TH immunoreactivity in the SNc of MDMA-treated mice and with a further decrease in the striatum and the SNc of MDMA + MPTP-treated mice compared with vehicle-treated, MDMA-treated, and MPTP-treated mice. The results demonstrate that chronic administration of MDMA during late adolescence in mice exacerbates the neurodegeneration and neuroinflammation caused by MPTP, suggesting that MDMA may constitute a risk factor for dopaminergic neuron degeneration.
authors.affiliation: Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Cagliari, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Costa
authors.forename: Lucia
authors.initials: L
authors.lastname: Frau
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Wardas
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pinna
authors.forename: Antonio
authors.initials: A
authors.lastname: Plumitallo
authors.forename: Micaela
authors.initials: M
authors.lastname: Morelli
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000473:pathology*; D039481:CD11b Antigen / Q000378:metabolism; D002452:Cell Count; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000473:pathology*; D004357:Drug Synergism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020267:MPTP Poisoning / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018759:Adrenergic Uptake Inhibitors; D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D014446:Tyrosine 3-Monooxygenase; D018817:N-Methyl-3,4-methylenedioxyamphetamine
keywords: CD11b; Parkinson's disease; basal ganglia; glial fibrillary acidic protein; neuroinflammation